Rebalanced hemostasis in liver disease: a misunderstood coagulopathy.

The combination of frequently abnormal hemostatic markers and catastrophic bleeding as seen with variceal hemorrhage has contributed to the longstanding misperception that chronic liver disease (CLD) constitutes a bleeding diathesis. Laboratory studies of hemostasis in liver disease consistently challenge this with global coagulation assays incorporating activation of the protein C pathway demonstrating rebalanced hemostasis. It is now recognized that bleeding in CLD is predominantly secondary to portal hypertension (rather than a coagulopathy) and additionally that these patients are at increased risk of venous thrombosis, particularly in the portal venous system. This narrative review describes the current understanding of hemostasis in liver disease, as well as the periprocedural management of hemostasis and anticoagulation for management of venous thromboembolism in patients with CLD.

Roberts LN 《-》

Bleeding and clotting disorders in pediatric liver disease.

Wicklund BM 《-》

Coagulopathy in liver disease: a balancing act.

Liver disease results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is rebalanced in chronic liver disease. The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High von Willebrand factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of bleeding. Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing bleeding risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of bleeding should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic patients undergoing invasive procedures but may increase the risk of thrombosis. Rebalanced hemostasis in liver disease is precarious and may be tipped toward hemorrhage or thrombosis depending on coexisting circumstantial risk factors. Bacterial infection may impair hemostasis in cirrhosis by triggering the release of endogenous heparinoids. There are no evidence-based guidelines for hemostatic therapy of acute hemorrhage in liver disease. There is currently inadequate evidence to support the use of recombinant FVIIa, prothrombin complex concentrates, or tranexamic acid in acute variceal or other hemorrhage.

Kujovich JL 《-》

Bleeding Risk and Management in Interventional Procedures in Chronic Liver Disease.

The coagulopathy of liver disease is distinctly different from therapeutic anticoagulation in a patient. Despite stable elevated standard clot-based coagulation assays, nearly all patients with stable chronic liver disease (CLD) have normal or increased clotting. Common unfamiliarity with the limitations of these assays in CLD may lead to inappropriate and sometimes harmful interventions, including blood product transfusions before a procedure. Knowledge of the distinct hemostatic alterations in CLD can allow identification of the small subset of patients with clinically significant coagulopathy who can benefit from hematologic optimization before invasive procedures.

DeAngelis GA ，Khot R ，Haskal ZJ ，Maitland HS ，Northup PG ，Shah NL ，Caldwell SH ... -  《-》

Hemostasis and thrombosis in patients with liver disease: the ups and downs.

Patients with chronic or acute liver failure frequently show profound abnormalities in their hemostatic system. Whereas routine laboratory tests of hemostasis suggest these hemostatic alterations result in a bleeding diathesis, accumulating evidence from both clinical and laboratory studies suggest that the situation is more complex. The average patient with liver failure may be in hemostatic balance despite prolonged routine coagulation tests, since both pro- and antihemostatic factors are affected, the latter of which are not well reflected in routine coagulation testing. However, this balance may easily tip towards a hypo- or hypercoagulable situation. Indeed, patients with liver disease may encounter both hemostasis-related bleeding episodes as well as thrombotic events. During the 3rd International Symposium on Coagulopathy and Liver disease, held in Groningen, The Netherlands (18-19 September 2009), a multidisciplinary panel of experts critically reviewed the current data concerning pathophysiology and clinical consequences of hemostatic disorders in patients with liver disease. Highlights of this symposium are summarized in this review.

Lisman T ，Caldwell SH ，Burroughs AK ，Northup PG ，Senzolo M ，Stravitz RT ，Tripodi A ，Trotter JF ，Valla DC ，Porte RJ ，Coagulation in Liver Disease Study Group ... -  《-》